The impact of clinical genome sequencing in a global population with suspected rare genetic disease.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

A rural doctor's telehealth training program during the COVID-19 pandemic.

INTRODUCTION: In Australia, remote consultations have been used as an adjunct to traditional healthcare delivery during the COVID-19 pandemic using telephone and video techniques with an increase in the use of telephone consultations, and to a lesser extent video consultations, for management of patient conditions, assessment, treatment, monitoring and diagnosis. METHODS: To establish the needs of rural doctors for training in the provision of remote consultations, an online survey of members of the Australian College of Rural and Remote Medicine was undertaken. Subsequently an online scenario-based training program was designed to improve the competencies of members in providing these consultations. The outcomes of this program were analysed using pre- and post-intervention surveys, and qualitative analysis of session recordings. RESULTS: The program improved trainee confidence and competence in providing safe, quality remote consultations, particularly when using video technologies. Competencies in communication, history taking, physical online examination, clinical management and professionalism improved. Trainees adapted their practice because they were then able to manage potential issues, were more aware of the capabilities of telehealth technologies and could assist a health professional, such as a nurse or Aboriginal Health Worker (with the patient) to do an examination. Concerns remained about set-up time, technical quality, privacy, interaction with and examination of patients, and how to assess the severity of conditions. CONCLUSION: The outcomes of the program showed significant improvement in the levels of confidence and competencies required for providing remote consultations using telehealth services. A need remains to improve virtual interactions with patients, and to acquire better technology and financial support for remote consultations. In an environment where government is asking whether remote consultations are appropriate and clinically effective, these findings provide guidance from a professional group of experienced rural practitioners.

Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation.

Conductive biomaterials offer promising solutions to enhance the maturity of cultured cardiomyocytes. While the conventional culture of cardiomyocytes on nonconductive materials leads to more immature characteristics, conductive microenvironments have the potential to support sarcomere development, gap junction formation, and beating of cardiomyocytes in vitro. In this study, we systematically investigated the behaviors of cardiomyocytes on aligned electrospun fibrous membranes composed of elastic and biodegradable polyurethane (PU) doped with varying concentrations of reduced graphene oxide (rGO). Compared to PU and PU-4%rGO membranes, the PU-10%rGO membrane exhibited the highest conductivity, approaching levels close to those of native heart tissue. The PU-rGO membranes retained anisotropic viscoelastic behavior similar to that of the porcine left ventricle and a superior tensile strength. Neonatal rat cardiomyocytes (NRCMs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on the PU-rGO membranes displayed enhanced maturation with cell alignment and enhanced sarcomere structure and gap junction formation with PU-10%rGO having the most improved sarcomere structure and CX-43 presence. hiPSC-CMs on the PU-rGO membranes exhibited a uniform and synchronous beating pattern compared with that on PU membranes. Overall, PU-10%rGO exhibited the best performance for cardiomyocyte maturation. The conductive PU-rGO membranes provide a promising matrix for in vitro cardiomyocyte culture with promoted cell maturation/functionality and the potential for cardiac disease treatment.

Recognition of a patient with neck autonomic dysfunction: findings from a rare case report of harlequin syndrome in direct access physiotherapy.

BACKGROUND: Harlequin syndrome is a rare autonomic condition consisting of unilateral facial flushing and sweating induced by heat, emotion or physical activity. The affected side presents anhidrosis and midline facial pallor due to denervation of the sympathetic fibers. CASE DESCRIPTION: This case describes a patient who reported right-side redness of the face associated with hyperhidrosis during physical activity. She had two previous major motor vehicle accidents. The patient demonstrated difficulties in the visual accommodation of the left eye, but cranial nerve assessment was unremarkable; the patient was then referred to an ophthalmologist, who excluded any autonomic dysfunction as the primary cause of convergence and visual acuity. OUTCOMES: A left-sided sympathetic dysfunction with Harlequin sign diagnosis was made followed by a progressive compensatory adaptation of the right face. The patient was educated and reassured about the benign nature of her problem. DISCUSSION: Knowledge of the autonomic nervous system is still limited in clinical practice. Although challenging, physiotherapists should develop the knowledge and ability needed to perform appropriate assessment of autonomic dysfunctions. CONCLUSION: A dispositional reasoning model should be considered in differential diagnosis.

Patient experiences and outcomes in a South Australian stand-alone Hospital in the Home program.

ObjectivesThis study aimed to compare clinical outcomes for patients admitted to Hospital in the Home (HITH) and traditional (bricks-and-mortar) hospitals and explore patient and carer experiences.MethodsA mixed methods approach including triangulation of quantitative and qualitative data was used. Quantitative outcomes were compared using augmented inverse propensity weighting to adjust for differences in patient characteristics between groups. Qualitative data was collected by focus groups and interviews and analysed using reflexive thematic analysis. The study took place in metropolitan Adelaide and one adjacent regional health network in 2020-22. Participants were patients discharged from either hospital setting with 1 of 22 eligible diagnoses. Hospital administrative data informed a comparison of outcomes that included mortality, rate of emergency department re-presentations and re-admissions, length of stay and incidence of complications.ResultsPatients treated in HITH were less unwell than traditional hospital patients. There were no safety or quality concerns identified in the clinical outcomes. Of 2095 HITH patients, the in-patient mortality rate was 0.2%, and 2.3% experienced a return to a bricks-and-mortar hospital during the HITH admission. For HITH patients, the mortality rate after 30days was lower (-1.3%, 95% CI -2 to -0.5, P=0.002), as were re-presentations in 28days (-7.2%, 95% CI -9.5 to -5, P<0.0001), re-admissions in 28days (-4.9%, 95% CI -6.7 to -3.2, P<0.001) and complications (-0.6%, 95% CI -0.8 to -0.5, P<0.001). Interviews of 35 patients and six carers found that HITH was highly accepted and preferred by patients. HITH was perceived to free up resources for other, more acutely unwell patients.ConclusionsHITH was preferred by patients and at least as effective in delivering quality health care as a traditional hospital, although the potential for unobserved confounding must be acknowledged.

Ursolic Acid Induces Beneficial Changes in Skeletal Muscle mRNA Expression and Increases Exercise Participation and Performance in Dogs with Age-Related Muscle Atrophy.

Muscle atrophy and weakness are prevalent and debilitating conditions in dogs that cannot be reliably prevented or treated by current approaches. In non-canine species, the natural dietary compound ursolic acid inhibits molecular mechanisms of muscle atrophy, leading to improvements in muscle health. To begin to translate ursolic acid to canine health, we developed a novel ursolic acid dietary supplement for dogs and confirmed its safety and tolerability in dogs. We then conducted a randomized, placebo-controlled, proof-of-concept efficacy study in older beagles with age-related muscle atrophy, also known as sarcopenia. Animals received placebo or ursolic acid dietary supplements once a day for 60 days. To assess the study's primary outcome, we biopsied the quadriceps muscle and quantified atrophy-associated mRNA expression. Additionally, to determine whether the molecular effects of ursolic acid might have functional correlates consistent with improvements in muscle health, we assessed secondary outcomes of exercise participation and T-maze performance. Importantly, in canine skeletal muscle, ursolic acid inhibited numerous mRNA expression changes that are known to promote muscle atrophy and weakness. Furthermore, ursolic acid significantly improved exercise participation and T-maze performance. These findings identify ursolic acid as a natural dietary compound that inhibits molecular mechanisms of muscle atrophy and improves functional performance in dogs.

Desigualdad educacional y socioeconómica como determinante de mortalidad en Chile: análisis de sobrevida en la cohorte del proyecto San Francisco / Socioeconomic and educational inequities as independent predictors for mortality in a developing country: A cohort study in San Francisco, Chile

Background: The socioeconomic position (SEP) and educational level of individuals have an inverse correlation with mortality in developed societies. Aim To assess in a society undergoing a socioeconomic transition, the mortality risk associated to a low SEP (combination of education and income, scale 0-25 points, reference > 10 points) and low education (education years, reference > 8 years), adjusting for other known risk factors. Material and methods: In this prospective cohort study, a random sample of 920 subjects, living in San Francisco de Mostazal, Chile, aged more than 20years (395 males) was examined for the first time in 1997-1999 and re-examined in 2005-2006. All had information about economic household income and level of education. A Cox regression model was used to evaluate the association between mortality and socioeconomic measures. Results: The crude mortality hazard ratio (HR) was 3.34 (95 percent confidence interval (CI) 2.88-3.87) and 6.05 (95 percent CI 5.04-7.26) for low SEP and low educational level, respectively. After adjusting for age, gender, hypertension, diabetes, dyslipidemia, abdominal obesity, smoking, alcohol intake and family history of cardiovascular disease, the figures were 1.23 (95 percent CI 1.04-1.43) and 1.54 (95 percent CI 1.23-1.85) for low SEP and low educational level, respectively. Conclusions: In a society in socioeconomic transition, low SEP and especially low educational level are risk factors for mortality even after adjusting for known mortality risk factors.

Mediciones antropométricas y riesgo de sufrir un evento cardiovascular no fatal en población chilena: resultados del proyecto San Francisco / Anthropometric indexes and risk of non-fatal cardiovascular events in a Chilean population: the San Francisco Project

Antecedentes: Varios índices antropométricos (IA) de obesidad han mostrado ser predictores de morbilidad cardiovascular en estudios epidemiológicos internacionales. Objetivo: Evaluar el impacto del índice de masa corporal (IMC), circunferencia de abdomen (CA), razón cintura/cadera (RCC), razón cintura/estatura (RCE) e índice pulso-masa (IPM) sobre el riesgo de sufrir un evento cardiovascular (ECV) en una cohorte de población chilena. Diseño: Estudio longitudinal de 920 personas (edad 39,5 +/- 16,3 años, 382 hombres) que participan en el proyecto San Francisco (PSF). Método: La población fue examinada entre 1997 y 1999 consignándose nivel socioeconómico (NSE), hipertensión arterial (HTA), diabetes, colesterol total, triglicéridos, tabaquismo, IMC > 30 kg/m2, CA > 102 cm en hombres y > 85 cm en mujeres, RCC > 1,00 en hombres y > 0,85 en mujeres, IPM > 1,00 y RCE > 0,53. Análisis de riesgo (RR) con intervalos de confianza al 95 por ciento (IC95 por ciento) y regresión logística mediante procedimiento stepwise. Resultados: Luego de 5,3 +/- 0,3 años de seguimiento se registraron 26 ECV resultando predictores: diabetes RR=4,48 (IC95 por ciento 1,87-10,7); HTA RR=5,16 (IC84 por ciento 2,27-11,71); bajo NSE RR=1,81 (IC95 por ciento 1,38-2,37); IMC RR=2,43 (IC95 por ciento 1,10- 5,37); CA RR=3,10 (IC95 por ciento 1,39-6,91) y RCE RR=6,58 (IC95 por ciento 1,96-22,1). En el análisis multivariado que incluyo con todos los IA controlados por edad y sexo, sólo la RCE fue predictor independiente con riesgo de 3,14 (p<0,01). En el modelo completo que incluyó todos los factores de riesgo analizados, sólo la edad, HTA, diabetes, RCE y bajo NSE predicen un ECV no fatal. Conclusión: En la cohorte de San Francisco la RCE aparece como un predictor simple e independiente de enfermedad cardiovascular con mejor desempeño que otros IA de obesidad. Sin embargo, puntos de corte específicos para población chilena deberían ser determinados y evaluados.

Background: International studies have shown that several obesity related anthropometric indices are associated to increased cardiovascular risk. Aim: To evaluate the risk of non-fatal cardiovascular events associated to body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) , pulse mass index (PMI) and waist-to-height ratio (WHtR) upon cardiovascular risk in a cohort of Chileans subjects. Methods: 920 subjects (age 39.5 +/- 16.3 years, 382 males) from the San Francisco Project were prospectively followed.From 1997 to 1999 we determined the socio-economic status (SES), the presence of hypertension, diabetes, cholesterol, and triglyceride levels, smoking status, obesity (BMI >30 kg/m2 , WC >102 for males and > 85 cm for females, WHR > 1 for males and > 0.85 for females, PMI >1 and WHtR > 0.53). Risk ratios and 95 percent confidence intervals (CI) along with stepwise logistic regression were used to assess statistical significance.Results: 26 cardiovascular events took place within 5.3+/-0.3 years of follow up. Significant predictive values were shown for diabetes (RR=4.8, CI 1.9-10.7), hypertension (RR=5.16, CI 2.27 – 11.7), low SEL(RR=1.81, CI 1.38-2.37), BMI (RR 2.43, CI 1.1-5.37), WC (RR=3.1, CI 1.39-6.91 and WHtR (RR = 6.58, CI 1.96-22.1). Logistic regression analysis indicated that only WHtR remained an independent predictor for cardiovascular events. After a different adjustment model, age, hypertension, diabetes, WHtR and low SES had predictive value for cardiovascular events. Conclusion: WHtR appears to be an independent marker for cardiovascular risk in the San Francisco cohort study. However, specific anthropometric cut-off points for chonic diseases in chilean subjets should be determined and tested.

Razón cintura-estatura: un mejor predictor antropométrico de riesgo cardiovascular y mortalidad en adultos chilenos: nomograma diagnóstico utilizado en el Proyecto San Francisco / Waist to height ratio: a better predictor of cardiovascular risk factors and mortality in Chilean adults: diagnostic nomograms from the San Francisco project

Antecedentes: Medidas antropométricas de adiposidad como índice de masa corporal (IMC), circunferencia de cintura (CC), razón cintura-cadera (RCC) y razón cintura-estatura (RCE) son conocidas por estar asociadas a factores de riesgo metabólico. Sin embargo, es controversial cual de ellas es mejor para predecir riesgo cardiovascular y mortalidad. Método: En este estudio de cohorte prospectivo con una muestra ponderada de 6714 hombres y 6340 mujeres, examinamos la relación entre índices antropométricos de adiposidad, factores de riesgo cardiovascular y mortalidad. Calculamos el área bajo la curva ROC (Receiving Operating Characteristic) evaluando el desempeño de cada índice para detectar hipertensión, diabetes o dislipidemia. El riesgo relativo de mortalidad con intervalos de confianza al95 por ciento (IC95 por ciento) fue calculado utilizando regresión logística controlando por edad y factores de riesgo. Resultados: En hombres, las áreas bajo la curva ROC para detectar uno o más factores de riesgo fueron: IMC 0.75 (0.74-0.77), CC 0.85 (0.84-0.86), RCC 0.80 (0.79-0.81) y RCE 0.90 (0.89-0.91). En mujeres esas áreas fueron 0,72 (0,71-0,74), 0,77 (0,76-0,79), 0,65 (0,63-0,66) y 0,81 (0,80-0,82) respectivamente. Durante 8 años de seguimiento (670 muertes, 362 hombres), el riesgo multivariado de mortalidad para IMC, CC, RCC y RCE fue en hombres 0,81 (0,58-1,10), 1,27 (0,93-1,74), 0,89 (0,66-1,21) y 2,37 (1,61-3,49) respectivamente. En mujeres, el riesgo para IMC, CC, RCC, RCE fue 0,95 (0,70-1,27), 1,35 (1,00-1,85), 1,54 (1,17-2,16), y 1,56 (1,13-2,26) respectivamente. Conclusiones: El ajuste de la CC por la estatura permite predecir con mayor precisión factores de riesgo cardiovascular y mortalidad. Se propone un nomograma para adultos chilenos.

Background: Several obesity anthropometric measures like body-mass-index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are known to be associated with metabolic risk factors. However, it remains controversial which of these markers is better to predict cardiovascular risk factors and mortality. Methods: In this prospective observational study with a weighted random sample of 6714 men and 6340 women (San Francisco de Mostazal, Chile), we examined the relation between obesity anthropometric measures, cardiovascular risk factors and all-cause mortality. We calculated area under curve ROC (Receiving Operating Characteristic) to evaluate performance of anthropometric measures for detecting one or more cardiovascular risk factors. Multivariate risks for mortality were calculated with logistic regression models controlling for age and cardiovascular risk factors. Results: In men, areas under curve ROC for detecting one or more risk factors at the baseline were: BMI 0.85 (0.74-0.77), WC 0.85 (0.84-0.86), WHR 0.80 (0.79-0.81) and WHtR 0.90 (0.89-0.91). In women, these areas were respectively 0,72 (0,71-0,74), 0,77 (0,76-0,79), 0,65 (0,63-0,66) and 0,81 (0,80-0,82). During 8 years of follow-up (670 deaths, 362 men), multivariate risks with 95 percent confidence intervals (95%CI) for BMI, WC, WHR, and WHtR were respectively in men 0,80 (0,58-1,10), 1,27 (0,93-1,74), 0,89 (0,66-1,21) and 2,37 (1,61-3,49). In women, multivariate risks for BMI, WC, WHR and WHtR were respectively 0,95 (0,70-1,27), 1,35 (1,00-1,85), 1,54 (1,17-2,16), and 1,56 (1,13-2,26). Conclusions: In this prospective cohort study, adjusting WC for body height was the best way for predicting cardiovascular risk factors and all-cause mortality in Chilean adults.

Razón cintura-estatura como un predictor de mortalidad en población chilena: un estudio de 8 años de seguimiento en la cohorte del proyecto San Francisco / Wais-to-height ratio to predict mortality in chilean adults: an 8 year follow-up studies

Antecedentes: Medidas antropométricas de obesidad como el índice de masa corporal (IMC), circunferencia de cintura (CC), razón cintura-cadera (RCC) y razón cintura-estatura (RCE) son conocidas por estar asociadas a factores de riesgo metabólico. Sin embargo, es controversial cuál de ellas es mejor para predecir mortalidad. Método: En este estudio prospectivo observacional, reclutamos 920 adultos sanos (>20 años, 395 hombres, San Francisco de Mostazal, Chile) y examinamos la relación entre medidas antropométricas de obesidad y mortalidad general utilizando puntos de corte población-específicos (IMC≥28 kg/m2 ambos sexos; CC≥92cm hombres, ≥88cm mujeres; RCC≥0,94 hombres, ≥0,84 mujeres y RCE≥0,55 ambos sexos). El riesgo relativo (RR) fue calculado utilizando regresión logística controlando por factores de riesgo cardiovascular convencionales. Además, calculamos el área bajo la curva ROC (Receiving Operating Characteristic) para evaluar el desempeño de cada medida antropométrica para predecir mortalidad. Resultados: Durante 8 años de seguimiento ocurrieron 47 muertes. En hombres, el RR con intervalos de confianza al 95 por ciento (IC95 por ciento) para IMC, CC, RCC y RCE fue 1.21 (0.93-1.58), 2.52 (1.86-3.40), 1.11 (0.86-3.20) y 3.38 (2.31-4.96) respectivamente. En mujeres, el RR fue 0.78 (0.60-1.01), 1.44 (1.07-1.93), 1.54 (1.13-2.10), y 1.56 (1.13-2.26) respectivamente. En hombres, las áreas bajo la curva ROC (IC95 por ciento) fueron: IMC 0.66 (0.65-0.68), CC 0.72 (0.71-0.74), RCC 0.72 (0.71-0.74) y RCE 0.77 (0.75-0.78). En mujeres, estas áreas fueron: 0.59 (0.57-0.61), 0.65 (0.63-0.67), 0.58 (0.56-0.60) y 0.70 (0.68-0.71) respectivamente.

Background: Several obesity anthropometric measures like body-mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are known to be associated with metabolic risk factors. However, it remains controversial which of these markers is better to predict mortality. Methods: In this prospective observational study, we enrolled 920 healthy adults (> years, 395 men, 98.7 percent Chilean-Hispanics living in San Francisco de Mostazal, Chile). We examined the relation between obesity anthropometric measures and all-cause mortality using population-specific cutoffs (BMI ≥28 kg/m2 both genders; WC ≥92 cm men, ≥88 cm women; WHR ≥0,94 men, 0,84 women and WHtR ≥0,55 both genders). Multivariate risks were calculated with logistic regression models controlling for cardiovascular and metabolic risk factors. In addition we calculated area under ROC curve (Receiving Operating Characteristic) to evaluate performance of every anthropometric measure to predict mortality. Results: Forty seven deaths occurred during 8 years of follow-up. In men, multivariate risks with 95 percent CI) for BMI, WC, WHR, and WHtR were respectively 1.21 (0.93-1.58), 2.52 (1.86-3.40), 1.11 (0.86-3.20) and 3.38 (2.31-4.96). In women, multivariate risk were respectively 0.78 (0.60-1.01). 1.44 (1.07-1.93), 1.54 (1.13-2.10), and 1.56 (1.13-2.26). In men, areas under curve ROC (95 percent CI) were BMI 0.66 (0.65-0.68), WC 0.72 (0.71-0.74), WHR 0.72 (0.71-0.74) and WHtR 0.77 (0.75-0.78). In women these areas were respectively 0.59 (0.57-0.61), 0.65 (0.63-0.67), 0.58 (0.56-0.60) and 0.70 (0.68-0.71). Conclusions: In this Chilean-Hispanic cohort WHtR is the most accurate predictor of all-cause mortality in comparison with other anthropometric measures of adiposity.

Resultados en 196 hernioplastias con técnica de Lichtenstein / Results in 196 hernioplasties using the Lichtenstein method

La hernioplastia con técnica de Lichtenstein (HL) ha tenido gran difusión por los buenos resultados que se han obtenido, por lo que fue incorporada a nuestro servicio el año 1997. el objetivo del presente trabajo es evaluar los resultados de esta técnica. Se revisan los antecedentes de 178 pacientes operados por Hernia Inguinal mediante HL, entre enero y diciembre de 1998. La muestra está constituida por 147 hombres (83 por ciento) y 31 mujeres (17 por ciento), con una edad promedio de 59 años y rango de 15 a 86. Se operaron un total de 196 hernias, de las cuales, directas fueron 83 (42 por ciento), indirectas 78 (40 por ciento), inguinoescrotales 12 (6 por ciento) y mixtas 12 (6 por ciento). En 11 pacientes (6 por ciento) la hernia era recidivada. En 115 (64 por ciento) casos se utilizó anestesia local, en 49 (28 por ciento) regional y en 14 (8 por ciento) general. La estadía intrahospitalaria promedio fue de 1,38 días y el 24 por ciento se operó en forma ambulatoria. El seguimiento fue de 62 por ciento, con un rango de 3 años y 6 meses a 4 años y 6 meses. Las complicaciones tardías fueron 1 neuralgia y 3 recidivas.